Inhibition of steroid sulfatase activity by danazol

K Carlström, Kjell Carlström, Anton Döberl, A Döberl, A Pousette, Åke Pousette, Gunnar Rannevik, G Rannevik, Nils Wilking, N Wilking
Acta obstetricia et gynecologica Scandinavica. Supplement · 1984 · vol. 63(S123) , pp. 107–111 · doi:10.3109/00016348409156994 · PMID:6238495 · W2102238665
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Danazol at therapeutic concentrations potently inhibits human steroid sulfatase activity in liver and breast tumor preparations, impacting estrogen formation from estrone sulfate.

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Abstract

The hydrolysis of dehydroepiandrosterone sulfate (DHAS) by human liver cells in culture and the hydrolysis of and formation of estradiol-17 beta (E2) from estrone sulfate (E1S) by human breast tumor preparations in vitro were studies in the presence and absence of danazol. In the latter tissue the effects of medroxyprogesterone acetate (MPA), trilostane, aminoglutethimide (AG) and tamoxifen were tested for comparison. Danazol at concentrations of 10(-6) - 1.4 X 10(-4) M strongly inhibited the hydrolysis of DHAS as well as the hydrolysis of and formation of E2 from E1S. With the exception of a slight inhibitory effect of trilostane upon E1S hydrolysis, the other four drugs did not inhibit the metabolism of E1S. Danazol, at concentrations corresponding to those occurring in vivo during therapy, is a potent inhibitor of steroid sulfatase activity. This may be one of the ways in which the drug affects peripheral and target tissue levels of steroid hormones.

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MeSH descriptors

Danazol Pregnadienes Aminoglutethimide Aminoglutethimide Breast Neoplasms Breast Neoplasms Carcinoma Carcinoma Culture Techniques Danazol Dehydroepiandrosterone Dehydroepiandrosterone Dehydroepiandrosterone Dehydroepiandrosterone Dehydroepiandrosterone Sulfate Dihydrotestosterone Dihydrotestosterone Dihydrotestosterone Estrogen Antagonists Estrogen Antagonists

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